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Scientists discover why a specific cancer drug is so effective

April 29, 2013

This image shows cancerous B cells that have been treated with rituximab. The protein CD20 (shown in green) has been drawn to the side of the cells. When the Natural Killer white blood cells approach they will stand an 80 percent chance of killing the cell if they latch on to the side where the protein has collected (credit: MCCIR)

Professor Daniel Davis and his team used high quality video imaging to investigate why the drug rituximab is so effective at killing cancerous B cells. It is widely used in the treatment of B cell malignancies, such as lymphoma and leukaemia — as well as in autoimmune diseases like rheumatoid arthritis.

Using high-powered laser-based microscopes, researchers made videos of the process by which rituximab binds to a diseased cell and then attracts white blood cells known as natural killer (NK) cells to attack.

They discovered that rituximab tended to stick to one side of the cancer cell, forming a cap and drawing a number of proteins over to that side. It effectively created a front and back to the cell — with a cluster of protein molecules massed on one side.

Natural born killers

But what surprised the scientists most was how this changed the effectiveness of natural killer cells in destroying these diseased cells. When the NK cell latched onto the rituximab cap on the B cell, it had an 80% success rate at killing the cell. In contrast, when the B cell lacked this cluster of proteins on one side, it was killed only 40% of the time.

Professor Davis says: “These results were really unexpected. It was only possible for us to unravel the mystery of why this drug was so effective, through the use of video microscopy. By watching what happened within the cells we could clearly identify just why rituximab is such an effective drug — because it tended to reorganize the cancerous cell and make it especially prone to being killed.”

He continues: “What our findings demonstrate is that this ability to polarize a cell by moving proteins within it should be taken into consideration when new antibodies are being tested as potential treatments for cancer cells. It appears that they can be up to twice as effective if they bind to a cell and reorganize it.”